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Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer.

Bauernhofer T, Kuss I, Friebe-Hoffmann U, Baum AS, Dworacki G, Vonderhaar BK, Whiteside TL - Br. J. Cancer (2003)

Bottom Line: In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004).Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006).Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis.

View Article: PubMed Central - PubMed

Affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.

ABSTRACT
Prolactin (PRL) has been reported to inhibit apoptosis in various cell types and to serve as a cofactor in the upregulation of CD25 on T cells during activation. We investigated a possible relation between prolactin receptor (PRL-R) or IL-2 receptor alpha (IL-2Ralpha, CD25) expression on circulating T lymphocytes and their apoptosis in patients with breast cancer. Peripheral blood mononuclear cells obtained from 25 patients, 25 normal controls (NC) and three cord blood samples were evaluated for Annexin V binding and expression of CD95, CD25, and PRL-R on CD3(+) T cells by multicolour flow cytometry. Plasma levels of PRL, sCD95L, and sIL-2R were determined in patients and controls and related to T-cell apoptosis. The ability of PRL to protect T cells from apoptosis induced by various agents was also studied. Expression of PRL-R on the surface of T cells was comparable in patients with breast cancer and NC, but PRL plasma levels in patients were significantly lower (P<0.05). In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004). Percentages of CD3(+)Fas(+) and CD3(+)CD25(+) cells were higher in the peripheral circulation of patients than NC (P<0.0001 and <0.04, respectively). Levels of sFasL were lowest in plasma of the patients with the highest proportions of CD3(+)Fas(+) T cells. Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006). Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis. These results indicate that expression of CD25 but not of PRL-R on the surface of activated T lymphocytes appears to be involved in modulating Fas/Fas - ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes and excessive turnover of immune cells in the circulation of patients with breast cancer.

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Expression of CD25 on CD3+ T cells (A) and Annexin V binding to CD25+ cells (B) in PBMC obtained from a representative patient with BC, a normal donor, or cord blood. Backgate was set on CD3+ cells. Three-colour flow cytometry was performed as described in Materials and Methods.
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fig5: Expression of CD25 on CD3+ T cells (A) and Annexin V binding to CD25+ cells (B) in PBMC obtained from a representative patient with BC, a normal donor, or cord blood. Backgate was set on CD3+ cells. Three-colour flow cytometry was performed as described in Materials and Methods.

Mentions: Proportions of CD25+CD3+Annexin V+ lymphocytes and MFI of CD25 expression in cord blood and in PBMC of normal controls and patients with breast cancer


Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer.

Bauernhofer T, Kuss I, Friebe-Hoffmann U, Baum AS, Dworacki G, Vonderhaar BK, Whiteside TL - Br. J. Cancer (2003)

Expression of CD25 on CD3+ T cells (A) and Annexin V binding to CD25+ cells (B) in PBMC obtained from a representative patient with BC, a normal donor, or cord blood. Backgate was set on CD3+ cells. Three-colour flow cytometry was performed as described in Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747567&req=5

fig5: Expression of CD25 on CD3+ T cells (A) and Annexin V binding to CD25+ cells (B) in PBMC obtained from a representative patient with BC, a normal donor, or cord blood. Backgate was set on CD3+ cells. Three-colour flow cytometry was performed as described in Materials and Methods.
Mentions: Proportions of CD25+CD3+Annexin V+ lymphocytes and MFI of CD25 expression in cord blood and in PBMC of normal controls and patients with breast cancer

Bottom Line: In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004).Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006).Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis.

View Article: PubMed Central - PubMed

Affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.

ABSTRACT
Prolactin (PRL) has been reported to inhibit apoptosis in various cell types and to serve as a cofactor in the upregulation of CD25 on T cells during activation. We investigated a possible relation between prolactin receptor (PRL-R) or IL-2 receptor alpha (IL-2Ralpha, CD25) expression on circulating T lymphocytes and their apoptosis in patients with breast cancer. Peripheral blood mononuclear cells obtained from 25 patients, 25 normal controls (NC) and three cord blood samples were evaluated for Annexin V binding and expression of CD95, CD25, and PRL-R on CD3(+) T cells by multicolour flow cytometry. Plasma levels of PRL, sCD95L, and sIL-2R were determined in patients and controls and related to T-cell apoptosis. The ability of PRL to protect T cells from apoptosis induced by various agents was also studied. Expression of PRL-R on the surface of T cells was comparable in patients with breast cancer and NC, but PRL plasma levels in patients were significantly lower (P<0.05). In patients, 18+/-11% (mean+/-s.d.) of CD3(+) cells bound Annexin V, compared to 9+/-6% in NC (P<0.0004). Percentages of CD3(+)Fas(+) and CD3(+)CD25(+) cells were higher in the peripheral circulation of patients than NC (P<0.0001 and <0.04, respectively). Levels of sFasL were lowest in plasma of the patients with the highest proportions of CD3(+)Fas(+) T cells. Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V(+) cells was significantly increased in patients compared to NC (P<0.006). Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis. These results indicate that expression of CD25 but not of PRL-R on the surface of activated T lymphocytes appears to be involved in modulating Fas/Fas - ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes and excessive turnover of immune cells in the circulation of patients with breast cancer.

Show MeSH
Related in: MedlinePlus